An efficient and convenient one-pot multicomponent synthesis of novel pyrimidine derivatives: N-(4-aryl-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamides

Article abstract of DOI:10.1007/s11164-012-0724-5

An efficient and facile synthesis of novel pyrimidine derivatives, N-(4-aryl-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamides, via one-pot multicomponent reaction of different aromatic aldehydes, 2-acetylpyridine, and cyanoguanidine in the presence of NaOH in anhydrous EtOH is reported. Pyrimidine derivatives are extremely important six membered aromatic heterocyclic rings containing two nitrogen atoms which have a wide variety of important biologically activity. This method has the advantages of easy work-up, convenient purification, short reaction times, and high yields.

Full text of DOI:10.1007/s11164-012-0724-5

Res Chem Intermed
DOI 10.1007/s11164-012-0724-5
An efficient and convenient one-pot multicomponent
synthesis of novel pyrimidine derivatives: N-(4-aryl-6-
(pyridin-2-yl)pyrimidin-2-yl)cyanamides
•
Liangce Rong Xianyong Wei Shimin Tao
•
•
•
Yao Lu Ruilun Xie Jun Zhou Zhimin Zong
•
•
Received: 20 May 2012 / Accepted: 8 July 2012
Ó Springer Science+Business Media B.V. 2012
Abstracts An efficient and facile synthesis of novel pyrimidine derivatives,
N-(4-aryl-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamides, via one-pot multicomponent
reaction of different aromatic aldehydes, 2-acetylpyridine, and cyanoguanidine in
the presence of NaOH in anhydrous EtOH is reported. Pyrimidine derivatives are
extremely important six membered aromatic heterocyclic rings containing two
nitrogen atoms which have a wide variety of important biologically activity. This
method has the advantages of easy work-up, convenient purification, short reaction
times, and high yields.
Keywords Multicomponent reaction Á N-((Pyridin-2-yl)pyrimidin-2-yl)cyanamide Á
2-Acetylpyridine Á Cyanoguanidine Á Synthesis
Introduction
Multicomponent reactions (MCRs) have emerged as efficient and powerful tools in
modern synthetic organic chemistry, because the synthesis of complex organic
molecules from simple and readily available substrates can be achieved in a very
fast and efficient manner without the isolation of any intermediates [1–6].
Therefore, developing new MCRs and improving known MCRs are popular areas
of research in current organic synthesis. Pyrimidine and its derivatives, for example
purines, pyrrolopyrimidines, pyrazolopyrimidines, etc., form parts the structures of
L. Rong Á X. Wei Á Y. Lu Á R. Xie Á J. Zhou Á Z. Zong
School of Chemical Engineering and Technology, China University of Mining and Technology,
Xuzhou 221006, Jiangsu, People’s Republic of China
L. Rong (&) Á S. Tao
College of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116,
Jiangsu, People’s Republic of China
e-mail: lcrong2005@yahoo.com
123

L. Rong et al.
many biologically active compounds and have many medical and biological
properties [7–10]. For example, 4H-pyrido[1,2-a]pyrimidin-4-ones have been used
as anticancer agents and HIV-integrase inhibitors [11, 12], and pteridines are potent
antitumor agents [13]. Although many kinds of pyrimidine derivative have been
prepared by use of different synthetic methods [14–18], it is still very essential to
find novel methods to prepare more new pyrimidine derivatives. In continuation of
our ongoing endeavors using MCRs for synthesis of organic compounds [19–21],
herein we report a practical and simple method of preparation of pyrimidine
derivatives by reaction of aromatic aldehydes, 2-acetylpyridine, and cyanoguanidine
under mild conditions.
Results and discussion
We have synthesized pyridylpyrimidine-2-amine in the presence of NaOH under
solvent-free conditions [22]. On the basis of this synthesis, we tried to prepare new
pyrimidines by three-component reaction of aldehyde, 2-acetylpyridines, and
cyanoguanidine in the presence of NaOH under solvent-free conditions. However,
we did not obtain the desired products.
We then investigated three-component reaction of 4-fluorobenzaldehyde 1a
(1 mmol), 2-acetylpyridines 2 (1 mmol), and cyanoguanidine 3 (1.5 mmol) as
model reaction with different solvents and different catalysts.
First, several alkaline and acidic catalysts were examined to set up the standard
reaction conditions. The experimental results showed that the acidic catalysts have
no effect of this reaction. However, we found the reaction could proceed
promisingly under basic conditions. A variety of basic catalysts, for example
NaOH, KOH, Na2CO3, K2CO3, Et3N, and DBU, were then examined in this model
reaction. We found weak inorganic bases, for example Na2CO3 and K2CO3, and
organic bases, for example Et3N and DBU, were not the efficient catalysts of this
synthesis. Strong inorganic bases, for example NaOH and KOH were sufficiently
active to promote this reaction.
Second, because solvents are generally important in multi-component reactions,
we also investigated the effect of solvent in this reaction. A variety of solvents, for
example anhydrous ethanol, methanol, DMF, acetonitrile, tetrahydrofuran, and
toluene, were tested in the model reaction under their respective reflux conditions
(DMF 80 °C). We found that this reaction proceeded smoothly in protonic solvents,
for example ethanol and methanol, but that non-protonic solvents, for example
acetonitrile and toluene, were unsuitable for this synthesis. The optimized results are
listed in Table 1. Taking into account the cost, toxicity, reaction time, and catalytic
properties of the catalysts and solvents, we chose NaOH and EtOH as the preferred
catalyst and solvent to conduct these syntheses.
Finally, we studied the model reaction at different temperatures. The reaction
was conducted at room temperature, 40, 50, 60, 70, 80, and 90 °C. The appropriate
temperature for this reaction was 80 °C; yields were not significantly improved by
use of higher temperatures (Table 2).
123

One-pot multicomponent synthesis of novel pyrimidine derivatives
Table 1 Synthesis of 4a in the
presence of different catalysts
and solvents
Entry
Catalyst
Et3N
Solvent
Time (h)
Yielda (%)
1
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
None
2
2
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1.5
2
3
8
5
2
C5H11N
3
DBU
0
4
MgCl2
FeCl3
0
5
0
6
ZnCl2
SnCl2
0
7
0
8
Na2CO3
K2CO3
Cs2CO3
KOH
25
28
21
87
0
9
10
11
12
13
14
15
16
17
18
19
20
21
22
KOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
None
0
EtOH
DMFb
THF
93
20
12
90
0
Reagents and conditions:
4-fluorobenzaldehyde 1a
(1 mmol), 2-acetylpyridine 2
(1 mmol), guanidine carbonate 3
(1.5 mmol), and NaOH
(2 mmol), solvent (10 mL),
reflux, anhydrous EtOH; bold
indicates the chosen catalyst and
solvent
MeOH
Toluene
CH3CN
EtOH
EtOH
EtOH
0
93
94
94
a
Isolated yields
b
Reaction temperature 80 °C
Table 2 Synthesis of 4a at
different temperatures
Entry
Catalyst
Temp. (°C)
Yielda (%)
1
2
3
4
5
6
7
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
r.t.
40
50
60
70
80
90
20
25
45
50
65
93
94
Bold indicates the best
temperature conditions
Under these optimized reaction conditions, a variety of aromatic aldehydes were
reacted with 2-acetylpyridine and cyanoguanidine in this three-component reaction
(Scheme 1). The results obtained are listed in Table 3. As shown in Table 3, fifteen
compounds were synthesized. Irrespective of whether electron-withdrawing (for
example F, Cl, Br) or electron-donating (for example CH3–, CH3O–) substituents
were present on the aromatic aldehydes, the products were obtained in high yield.
The properties of the substituent groups had no obvious effect on these reactions.
1
All the new target compounds were completely characterized by IR, H NMR,
13C NMR, and HRMS. For example, the 1H NMR spectrum of 4i contains a singlet
123

L. Rong et al.
R
N
O
CHO
NH
NHCN
NaOH
C2H5OH
CH3
+
+
R
H2N
N
N
NHCN
N
1
2
3
4
Scheme 1 Synthesis of N-(4-aryl-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamides
Table 3 Results from synthesis
of compounds 4
Entry
R
Product
Yields (%)
1
2-F
4a
4b
4c
4d
4e
4f
93
91
90
93
95
94
93
92
94
96
93
91
91
94
93
2
3-F
3
4-F
4
2-Br
5
4-Br
6
4-Cl
7
2,4-Cl2
3,4-Cl2
4-CH3
4g
4h
4i
8
9
10
11
12
13
14
15
3,4-(CH3)2
3-CH3O
2,5-(CH3O)2
3,4-(CH3O)2
3,4,5-(CH3O)3
3,4-OCH2O
4j
4k
4l
4m
4n
4o
at delta 2.37 from the CH3 protons and a singlet at delta 11.64 from the NHCN
protons. The spectrum also contains doublets at delta 7.35 ppm (J = 7.6 Hz),
8.35 ppm (J = 7.5 Hz), and 8.78 ppm (J = 6.9 Hz), a multiplet at delta
8.01–8.09 ppm, and a triplet at delta 7.59 ppm (J = 5.1 Hz) from the nine aryl
protons. In 13C NMR, the chemical shifts of the 17 carbon atoms were at 20.98,
106.14, 110.53, 121.38, 127.02, 129.59, 132.56, 137.60, 141.69, 149.64, 152.40,
158.86, 164.42, and 165.72. In the HRMS spectrum, the calculated m/z for
C17H13N5 [M ? Na]? is 310.1069, and we found m/z is 310.1046.
Conclusions
An efficient one-pot multi-component reaction has been developed for synthesis of
N-(4-aryl-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamides from simple and readily avail-
able starting materials in the presence of NaOH in ethanol. The products are novel
tridentate ligands that can be used to construct important metal–organic complexes
123

One-pot multicomponent synthesis of novel pyrimidine derivatives
(coordination compounds). The method has many advantages, for example mild
conditions, inexpensive reagents, easily obtained catalyst, short reaction time, and
high yields.
Experimental
Melting points were determined on XT-5 melting-point apparatus with microscope
and are uncorrected. IR spectra were recorded on a FT Bruker Tensor 27
spectrometer. 1H NMR and 13C NMR spectra were obtained from solution in
CDCl3, with Me4Si as internal standard, using a Bruker-300 spectrometer. HRMS
spectra were obtained with a Bruker microTOF-Q 134 instrument.
General procedure for synthesis of N-(4-aryl-6-(pyridin-2-yl)pyrimidin-
2-yl)cyanamide derivatives
The mixture of aromatic aldehyde 1 (1 mmol), 2-acetylpyridine 2 (1 mmol), cyano
guanidine 3 (1.5 mmol), and NaOH (2 mmol) was placed in a reaction flask with
anhydrous EtOH and heated at \80 °C for approximately 1 h. After completion of
the reaction, the mixture was poured into water (0.5 % HCl), and then washed
thoroughly with water. The product was isolated by filtration, dried, and
recrystallized from 95 % ethanol.
N-(4-(2-Fluorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4a)
m.p. 211–212 °C; IR (KBr) m: 3,370, 2,925, 2,361, 2,341, 2,187, 1,683, 1,610,
1,523, 1,489, 1,458, 1,430, 1,312, 1,220, 1,102, 1,023, 993, 770, 711, 670 cm-1; 1H
NMR (300 MHz, CDCl3) d: 7.37–7.45 (3H, m, ArH), 7.59–7.65 (2H, m, ArH),
8.03–8.14 (2H, m, ArH), 8.41 (1H, d, J = 1.8 Hz, ArH), 8.79 (1H, d, J = 4.2 Hz,
ArH), 11.80 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 110.47, 116.71,
119.58, 121.45, 125.08, 130.58, 133.36, 137.56, 149.79, 152.20, 155.46, 158.93,
162.36, 164.69, 164.75.
HRMS m/z calculated for C16H10FN5 [M ? Na]?: 314.0818, found: 314.0810.
N-(4-(3-Fluorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4b)
m.p. 198–199 °C; IR (KBr) m: 3,365, 2,932, 2,360, 2,341, 1,716, 1,651, 1,541,
1
1,488, 1,353, 1,242, 774, 669 cm-1; H NMR (300 MHz, CDCl3) d: 7.43 (1H, t,
J = 6.3 Hz, ArH), 7.61–7.66 (2H, m, ArH), 7.99 (1H, d, J = 8.1 Hz, ArH),
8.06–8.09 (2H, m, ArH), 8.37 (1H, d, J = 5.7 Hz, ArH), 8.47 (1H, s, ArH), 8.79
(1H, d, J = 3.3 Hz, ArH), 11.77 (1H, s, NHCN). 13C NMR (400 MHz, DMSO) d:
110.35, 106.87, 110.00, 112.72, 113.54, 118.08, 121.41, 125.94, 130.79, 137.53,
149.39, 152.27, 158.73, 161.28, 164.36.
HRMS m/z calculated for C16H10FN5 [M ? H]?: 292.0998, found: 292.0994.
123

L. Rong et al.
N-(4-(4-Fluorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4c)
m.p. 160–161 °C; IR (KBr) m: 3,350, 2,839, 2,360, 2,341, 2,251, 1,716, 1,651,
1,604, 1,540, 1,507, 1,487, 1,411, 1,362, 1,235, 1,154, 1,097, 836, 777, 669,
1
570 cm-1; H NMR (300 MHz, CDCl3) (d, ppm): 7.47 (2H, t, J = 8.4 Hz, ArH),
7.62 (1H, s, ArH), 8.06 (1H, t, J = 6.0 Hz, ArH), 8.28 (2H, s, ArH), 8.36 (1H, d,
J = 7.8 Hz, ArH), 8.42 (1H, s, ArH), 8.69 (1H, s, ArH), 11.77 (1H, s, NHCN). 13
C
NMR (300 MHz, CDCl3) d: 106.46, 110.42, 116.04, 121.46, 126.24, 129.74,
131.95, 137.69, 149.69, 152.34, 158.91, 162.55, 164.81, 165.86.
HRMS m/z calculated for C16H10FN5 [M ? H]?: 292.0998, found: 292.0980.
N-(4-(2-Bromophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4d)
m.p. 182–183 °C; IR (KBr) m: 3,350, 2,980, 2,360, 2,341, 1,748, 1,716, 1,698,
1,651, 1,540, 1,507, 1,473, 1,456, 1,418, 1,340, 773, 669, cm-1 1H NMR
;
(300 MHz, CDCl3) d: 7.50–7.56 (1H, m, ArH), 7.59–7.63 (1H, m, ArH), 7.78 (1H,
d, J = 7.8 Hz, ArH), 8.05 (1H, t, J = 7.5 Hz, ArH), 8.18 (1H, d, J = 6.9 Hz, ArH),
8.35 (2H, d, J = 7.8 Hz, ArH), 8.43 (1H, d, J = 8.7 Hz, ArH), 8.78 (1H, d,
J = 3.3 Hz, ArH), 11.76 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 106.96,
110.27, 121.50, 126.16, 126.24, 126.29, 129.55, 131.18, 134.14, 137.70, 149.68,
152.22, 158.90, 164.24, 164.97.
HRMS m/z calculated for C16H10BrN5 [M ? H]?: 352.0198, found: 352.0188.
N-(4-(4-Bromophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4e)
m.p. 181–182 °C; IR (KBr) m: 3,365, 2,988, 2,360, 2,341, 2,249, 1,716, 1,698,
1,647, 1,540, 1,474, 1,421, 1,399, 1,360, 1,072, 1,008, 830, 794, 777, 670 cm-1; 1H
NMR (300 MHz, CDCl3) d: 7.64 (1H, t, J = 6.0 Hz, ArH), 7.81 (2H, d,
J = 8.4 Hz, ArH), 8.06–8.12 (1H, m, ArH), 8.19 (2H, d, J = 8.7 Hz, ArH), 8.39
(1H, d, J = 7.8 Hz, ArH), 8.49 (1H, s, ArH), 8.81 (1H, d, J = 3.9 Hz, ArH), 11.79
(1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 103.20, 106.70, 118.30, 121.52,
125.09, 129.16, 132.11, 137.79, 144.38, 149.77, 151.50, 152.31, 155.30, 164.80.
HRMS m/z calculated for C16H10BrN5 [M ? H]?: 352.0198, found: 352.0163.
N-(4-(4-Chlorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4f)
m.p. 180–181 °C; IR (KBr) m: 3,351, 2,955, 2,360, 2,341, 1,716, 1,652, 1,541,
1,362, 832, 791, 778, 669 cm-1; 1H NMR (300 MHz, CDCl3) d: 7.62–7.67 (3H, m,
ArH), 8.05–8.11 (1H, m, ArH), 8.23–8.27 (2H, m, ArH), 8.39 (1H, d, J = 8.1 Hz,
ArH), 8.47 (1H, d, J = 3.9 Hz, ArH), 8.80 (1H, d, J = 3.6 Hz, ArH), 11.79 (1H, s,
NHCN). 13C NMR (300 MHz, CDCl3) d: 102, 26, 110.30, 121.51, 126.35, 128.89,
129.16, 134.14, 136.45, 137.78, 141.60, 149.75, 152.28, 158.92, 165.20, 166.73.
HRMS m/z calculated for C16H10ClN5 [M ? H]?: 308.0703, found: 308.0685.
123

One-pot multicomponent synthesis of novel pyrimidine derivatives
N-(4-(2,4-Dichlorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4g)
m.p. 205–206 °C; IR (KBr) m: 3,360, 2,840, 2,360, 2,341, 2,239, 1,716, 1,652,
1,590, 1,557, 1,539, 1,474, 1,419, 1,375, 1,354, 1,231, 1,105, 1,052, 1,002, 868,
1
843, 819, 781, 747, 721, 669, 574 cm-1; H NMR (300 MH, CDCl3) d: 7.61–7.67
(2H, m, ArH), 7.77 (1H, d, J = 8.4 Hz, ArH), 7.85 (1H, d, J = 3.6 Hz, ArH),
8.07–8.12 (1H, m, ArH), 8.27 (1H, s, ArH), 8.41 (1H, d, J = 7.8 Hz, ArH), 8.79
(1H, d, J = 4.2 Hz, ArH), 11.94 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d:
102.26, 105.14, 107.44, 109.73, 110.89, 111.62, 112.40, 121.58, 127.94, 132.65,
137.87, 143.84, 149.88, 152.04, 154.09, 165.03.
HRMS m/z calculated for C16H9Cl2N5 [M ? Na]?: 364.0133, found: 364.0114.
N-(4-(3,4-Dichlorophenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4h)
m.p. 180–181 °C; IR (KBr) m: 3,370, 2,985, 2,360, 2,341, 2,250, 1,748, 1,716,
1
1,698, 1,647, 1,540, 1,488, 1,424, 1,361, 1,092, 832, 777, 669 cm-1; H NMR
(300 MHz, CDCl3) d: 7.60–7.65 (2H, m, ArH), 8.02–8.09 (1H, m, ArH), 8.23 (2H,
d, J = 8.7 Hz ArH), 8.37 (1H, d, J = 8.4 Hz, ArH), 8.43 (1H, s, ArH), 8.78 (1H, d,
J = 3.9 Hz, ArH), 11.74 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 106.61,
110.35, 121.47, 126.28, 128.90, 129.00, 134.24, 136.42, 137.70, 149.70, 152.28,
158.96, 164.65, 164.87, 164.89.
HRMS m/z calculated for C16H9Cl2N5 [M ? Na]?: 364.0133, found: 364.0168.
N-(4-(Pyridin-2-yl)-6-p-tolylpyrimidin-2-yl)cyanamide (4i)
m.p. 168–169 °C; IR (KBr) m: 3,370, 3,153, 2,361, 2,341, 2,233, 1,699, 1,684,
1,653, 1,597, 1,578, 1,539, 1,507, 1,458, 1,457, 1,420, 1,347, 1,232, 825, 800, 778,
1
721, 669 cm-1; H NMR (300 MHz, CDCl3) d: 2.37 (3H, s, CH3), 7.35 (2H, d,
J = 7.8 Hz, ArH), 7.59 (1H, t, J = 5.1 Hz, ArH), 8.01–8.09 (3H, m, ArH), 8.35
(2H, d, J = 7.5 Hz, ArH), 8.78 (1H, d, J = 6.9 Hz, ArH), 11.64 (1H, s, NHCN).
13C NMR (300 MHz, CDCl3) d: 20.98, 106.14, 110.35, 121.38, 126.13, 127.02,
129.59, 129.69, 132.56, 137.60, 141.69, 149.64, 149.70, 152.40, 158.86, 164.42,
165.72.
HRMS m/z calculated for C17H13N5 [M ? Na]?: 310.1069, found: 310.1046.
N-(4-(3,4-Dimethylphenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4j)
m.p. 122–123 °C; IR (KBr) m: 3,366, 2,980, 2,360, 2,341, 2,227, 1,646, 1,575,
1
1,557, 1,539, 1,506, 1,472, 1,456, 1,418, 1,351, 1,090, 994, 775, 668 cm-1; H
NMR (300 MHz, CDCl3) d: 2.29 (3H, s, CH3), 2.31 (3H, s, CH3), 7.31 (1H, d,
J = 8.1 Hz, ArH), 7.62–7.34 (1H, q, J = 7.8 Hz, ArH), 7.92 (1H, d, J = 7.8 Hz,
ArH), 7.96 (1H, s, ArH), 8.03–8.09 (1H, m, ArH), 8.36 (1H, s, ArH), 8.38 (1H, s,
ArH), 8.79 (1H, d, J = 4.2 Hz, ArH), 11.70 (1H, s, NHCN). 13C NMR (300 MHz,
CDCl3) d: 19.39, 102.27, 106.12, 110.63, 121.41, 124.63, 126.16, 127.91, 130.12,
132.91, 137.04, 137.65, 140.52, 140.55, 149.66, 152.47, 158.92, 165.91.
HRMS m/z calculated for C18H15N5 [M ? Na]?: 324.1225, found: 324.1204.
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L. Rong et al.
N-(4-(3-Methoxyphenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4k)
m.p. 164–165 °C; IR (KBr) m: 3,343, 2,980, 2,361, 2,250, 1,717, 1,698, 1,648,
1,541, 1,508, 1,488, 1,457, 1,420, 1,352, 1,285, 1,262, 1,247, 1,045, 796, 770,
;
670 cm-1 1H NMR (300 MHz, CDCl3) d: 3.84 (3H, s CH3O), 7.14 (1H, dd,
J = 2.1 Hz, J = 8.1 Hz, ArH), 7.46 (1H, t, J = 8.1 Hz, ArH), 7.59 (1H, dd,
J = 2.1 Hz, J = 6.9 Hz, ArH), 7.68 (1H, s, ArH), 7.74 (1H, d, J = 7.8 Hz, ArH),
8.03 (1H, t, J = 7.8 Hz, ArH), 8.36 (2H, d, J = 10.2 Hz, ArH), 8.77 (1H, d
J = 7.5 Hz, ArH), 11.66 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 55.22,
106.78, 110.41, 112.11, 112.16, 117.21, 119.45, 121.44, 126.15, 130.11, 136.82,
137.58, 149.64, 149.70, 152.35, 158.80, 159.63, 164.65, 165.56.
HRMS m/z calculated for C17H13N5O [M ? Na]?: 326.1018, found: 326.0968.
N-(4-(2,5-Dimethoxyphenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4l)
m.p. 185–186 °C; IR (KBr) m: 3,316, 3,145, 2,999, 2,360, 2,341, 2,181, 1,683,
1,642, 1,594, 1,522, 1,497, 1,466, 1,432, 1,396, 1,311, 1,282, 1,246, 1,220, 1,194,
1,159, 1,101, 1,016, 802, 770, 723, 711 cm-1; 1H NMR (300 MHz, CDCl3) d: 3.70
(3H, s, OCH3), 3.79 (3H, s, OCH3), 6.76 (1H, d, J = 3.0 Hz, ArH), 6.89 (1H, dd,
J = 3.0 Hz, J = 8.7 Hz, ArH), 7.02 (1H, d, J = 9.0 Hz, ArH), 7.41–7.45 (1H, m,
ArH), 7.89 (2H, dt, J = 1.2 Hz, J = 5.7 Hz, ArH), 8.63 (1H, d, J = 3.3 Hz, ArH),
8.95 (1H, s, ArH), 11.70 (1H, s, NHCN). 13C NMR (300 MHz, CDCl3) d: 55.40,
55.16, 101.64, 112.51, 112.71, 113.38, 116.97, 119.47, 124.01, 130.45, 131.00,
137.39, 137.41, 147.98, 148.44, 149.95, 153.34, 155.92.
HRMS m/z calculated for C18H15N5O2 [M ? Na]?: 356.1123, found: 356.1142.
N-(4-(3,4-Dimethoxyphenyl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4m)
m.p. 193–194 °C; IR (KBr) m: 3,296, 2,360, 2,341, 2,235, 2,181, 1,599, 1,577,
1,539, 1,519, 1,506, 1,419, 1,376, 1,353, 1,318, 1,263, 1,214, 1,174, 1,132, 1,019,
1
871, 818, 779, 765, 669, 600 cm-1; H NMR (300 MHz, CDCl3) d: 3.94 (3H, s,
OCH3), 3.97 (3H, s, OCH3), 6.93 (1H, d, J = 6.3 Hz, ArH), 7.45–7.48 (1H, m,
ArH), 7.78 (2H, d, J = 6.0 Hz, ArH), 7.87–7.91 (1H, m, ArH), 8.20 (1H, s, ArH),
8.37 (1H, d, J = 5.7 Hz, ArH), 8.79 (1H, d, J = 3.3 Hz, ArH). 13C NMR
(300 MHz, CDCl3) d: 55.50, 55.97, 109.90, 110.80, 115.40, 119.44, 121.23, 122.18,
125.88, 127.92, 137.40, 149.18, 149.50, 152.33, 158.43, 165.61.
HRMS m/z calculated for C18H15N5O2 [M ? Na]?: 356.1123, found: 356.1105.
N-(4-(Pyridin-2-yl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-2-yl)cyanamide (4n)
m.p. 229–230 °C; IR (KBr) m: 3,330, 2,942, 2,360, 2,340, 1,601, 1,581, 1,540,
1,470, 1,455, 1,424, 1,373, 1,345, 1,248, 1,220, 1,126, 985, 855, 797, 777, 741, 697,
658 cm-1 1H NMR (300 MHz, CDCl3) d: 3.96 (3H, s OCH3), 4.01 (6H, s
;
2 9 OCH3), 7.48–7.51 (3H, m, ArH), 7.93 (1H, t, J = 5.7 Hz, ArH), 8.42 (1H, s,
ArH), 8.50 (1H, d, J = 5.2 Hz, ArH), 8.78–8.80 (1H, m, ArH). 13C NMR
123

One-pot multicomponent synthesis of novel pyrimidine derivatives
(300 MHz, CDCl3) d: 56.50, 60.59, 104.99, 105.02, 122.03, 126.63, 133.11, 138.11,
140.97, 150.12, 153.60, 159.17, 165.02.
HRMS m/z calculated for C19H17N5O3 [M ? Na]?: 386.1229, found: 386.1228.
N-(4-(Benzo[d][1,3]dioxol-5-yl)-6-(pyridin-2-yl)pyrimidin-2-yl)cyanamide (4o)
m.p. 225–226 °C; IR (KBr) m: 3,335, 2,909, 2,360, 2,341, 1,601, 1,585, 1,537,
1,504, 1,488, 1,445, 1,426, 1,384, 1,364, 1,332, 1,267, 1,243, 1,213, 1,110, 1,093,
1,040, 932, 852, 824, 789, 775, 671 cm-1; 1H NMR (300 MHz, CDCl3) d: 6.16 (2H,
s, OCH2O), 7.10 (1H, d, J = 8.4 Hz, ArH), 7.60 (1H, dd, J = 5.1 Hz, J = 6.6 Hz,
ArH), 7.72 (1H, s, ArH), 7.82 (1H, d, J = 8.1 Hz, ArH), 8.06 (1H, t, J = 7.8 Hz,
ArH), 8.35 (2H, d, J = 8.4 Hz, ArH), 8.79 (1H, d, J = 4.5 Hz, ArH), 11.62 (1H, s,
NHCN). 13C NMR (300 MHz, CDCl3) d: 101.89, 106.71, 108.64, 121.90, 122.41,
126.13, 129.46, 137.64, 137.68, 137.71, 148.06, 148.12, 149.65, 150.33, 158.68,
165.22.
HRMS m/z calculated for C17H11N5O2 [M ? H]?: 318.0991, found: 318.0978.
Acknowledgments This work was supported by National Natural Science Foundation of China (NSFC)
(21172188), Foundation of Xuzhou Normal University (10XLS02) and Priority Academic Program
Development of Jiangsu Higher Education Institutions.
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